Protein exchange and self recognition in myxobacteria biofilms

描述（由申请方提供）：生物膜是表面附着的微生物群落，在感染部位占主导地位，并且具有非常重要的医学意义，因为它们抵抗抗生素和免疫系统的杀灭。了解生物膜细胞如何相互作用以引起表型变化的进展受到有限的策略来探测它们的细胞相互作用的阻碍。在这里，我们试图通过描述一个新的过程来填补知识空白，在这个过程中，生物膜内的细胞交换它们的外膜（OM）脂蛋白，从而导致表型变化。我们的模式生物，粘球菌xanthus，是一种社会革兰氏阴性细菌，可以进行多细胞发育，是用来探测生物膜细胞动力学。在初步结果中，我们现在表明，OM也交换，我们确定了转移所需的细胞蛋白质。我们还表明，转移，这只发生在结构化的生物膜，涉及亲属识别，使细胞区分自己从其他密切相关的M。黄藓属分离物由于转移涉及OM材料的大量移动，我们认为这种交换过程是细胞交流和共享资源的合作行为的一种形式。最后，我们表明转移调节群体扩张，并可能介导的纳米管结构。我们的研究结果具有广泛的影响，因为真核细胞是众所周知的交换细胞成分，在细菌系统中，蛋白质交换开始被理解为一个普遍的过程，涉及通信和不同的细胞过程。我们的遗传系统已经做好了充分准备来解决这些基本问题。在这里，在目标1中，我们将使用遗传方法来识别参与转移的蛋白质的细胞补体，并定义它们的相互作用和纳米管在转移中可能发挥的作用。目的2将描述亲属识别转移的机制，并确定细胞-细胞识别的遗传决定因素。目的3将确定OM交换如何调节游泳扩展和它可能在发育和包膜稳态中发挥的作用。这些综合努力将推进我们对生物膜细胞如何相互作用、相互识别和交换细胞物质的机械理解，这导致了与分离或分离的细胞不同的表型变化。 公共卫生相关性：生物膜是密集的微生物垫，在医学上很重要，因为它们是大多数微生物感染的原因。生物膜感染治疗困难且昂贵，因为它们对宿主免疫系统和抗菌剂具有抗性。该提案旨在研究生物膜中新的细胞相互作用，这可能会促进我们对生物膜的理解，从而改善干预策略。

DESCRIPTION (provided by applicant): Biofilms are surface attached microbial communities that predominates infection sites, and are of keen medical importance as they resist killing by antibiotics and the immune system. Progress in understanding how biofilm cells interact to elicit phenotypic changes has been impeded by limited strategies to probe their cellular interactions. Here, we seek to fill-in knowledge gaps by describing a novel process where cells within biofilms exchange their outer membrane (OM) lipoproteins, which result in phenotypic changes. Our model organism, Myxococcus xanthus, is a social gram-negative bacterium that can undergo multicellular development, is used to probe biofilm cellular dynamics. In preliminary results we now show that OMs are also exchanged and we identify cellular proteins required for transfer. We also show that transfer, which only occurs in structured biofilms, involves kin recognition whereby cells distinguish themselves from other closely related M. xanthus isolates. As transfer involves costly bulk movement of OM material, we believe this exchange process is a form of cooperative behavior where cells communicate and share resources. Lastly, we show transfer regulates swarm expansion and may be mediated by nanotube structures. Our results have broad implications as eukaryotic cells are widely known to exchange cellular components, and in bacterial systems, protein exchange is beginning to be appreciated as a prevalent process involved in communication and diverse cellular processes. Our genetic system is well poised to tackle these fundamental issues. Here, in Aim 1 we will use genetic approaches to identify the cellular complement of proteins involved in transfer, and define their interactions an the role nanotubes might play in transfer. Aim 2 will characterize the mechanism of kin recognition in transfer and define the genetic determinant for cell-cell recognition. Aim 3 will determine how OM exchange regulates swam expansion and a role it might play in development and envelope homeostasis. These combined efforts will advance our mechanistic understanding of how biofilm cells interact, recognize one another and exchange cellular material, which results in phenotypic changes that are distinct from planktonic or isolated cells. PUBLIC HEALTH RELEVANCE: Biofilms are dense microbial mats that are medically important as they account for most microbial infections. Biofilm infections are difficult and expensive to treat because they are resistant to the host immune system and antimicrobial agents. This proposal seeks to investigate novel cell interactions in biofilms, which may advance our understanding of biofilms and consequently lead to improved intervention strategies.